Interruption in the continuity of an axon initiates multiple changes (the axon reaction) within the cell body. The precise cellular event or events which mediate and signal the axon reaction are unknown. Candidates include alteration in intercellular interactions (axon/target, or axon/ensheathing cells) and intraneuronal interactions (perikaryon/axon terminal). The underlying premise of this project is that understanding the conditions in which specific aspects of the axon reaction are, or are not, elicited will provide important clues to the interactions which influence perikaryal behavior in normal and diseased motor neurons. We will study specific aspects, or "markers" of the axon reaction which are quantifiable and have presumptive biologic meaning. After completing the development of a new experimental system which surmounts previous technical restrictions on this line of research, the focus will be on two interrelated aspects of the axon reaction. I. Characterize the response of specific "markers" of the axon reaction with respect to changes in the location of axonal injury. This will serve two purposes. 1) It will provide essential data for later studies about the maximum response possible for each "marker". 2) The sensitivity of each marker's response to changes in location of axonal injury is itself a clue as to possible regulator influences. II. Characterize the pattern of response of these different axon reaction "markers" to different experimental manipulations of axon and target muscle. By controlling the physiologic circumstances in which aspects of the axon reaction are evoked, we can focus on the specific intercellular or intraneuronal interactions which have the most influence on perikaryal function.